Detachment of the neural retina from the retinal pigmented epithelium is a serious cause of visual loss. The retina has a remarkable ability to recover upon reattachment, although visual recovery, when the macula is involved, is often less than optimal. We have discovered over the course of this project that detachment initiates a complex series of biochemical and structural changes throughout the retina, including significant remodeling of both neurons and glia. We have also discovered that reattachment initiates its own set of changes beyond outer segment recovery, including rod neurite sprouting and the growth of Muller cells onto the vitreal surface of the retina. We have also discovered that the simple breathing of oxygen-enriched air can mitigate many of the degenerative changes associated with detachment. The better we understand these complex cellular responses and eventually the molecular mechanism underlying them, the better our position to developing new therapeutic approaches to this and other retinal degenerations becomes. The specific aims for this project are: 1) To study neuronal and glial remodeling in short and long-term detachments and reattachments and the effect of this remodeling on retinal circuitry. 2) To test the hypothesis that the intraretinal proliferative response induced by detachment produces a population of multipotent progenitor cells, and to determine the fate of the proliferating ceils. 3) To test the hypothesis that inhibiting this response will reduce the production of subretinal and/or epiretinal membranes (PVR) and alter the course of degeneration induced by detachment. 4) To test the hypothesis that hyperoxia will improve the cellular outcome of retinal reattachment. 5) To develop a mouse model of detachment and to study mice deficient in the two intermediate filament proteins, GFAP and vimentin to determine their roles in glial cell responsiveness to detachment. [unreadable] [unreadable]